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Tumor Cells Break Free at Snail's Pace

The deadliest tumors seed the body with sloughed cells, which can take root and form new tumors. Researchers have now identified a family of proteins, called Snail, that helps cancer cells pull up stakes. Doctors might one day look for these proteins as warning flags of tumors that are most likely to spread.

Snail isn't all bad. During embryonic development, these proteins direct tissue to turn into mesenchymal cells, such as blood, lymph, or neurons. Now two teams have shown that Snail interferes with the gene for E-cadherin. This protein turns developing tissue into epithelial cells, which pack together tightly to form organs such as the bladder, ovaries, and lungs. E-cadherin is a kind of glue that sticks cells together; tumors with low E-cadherin levels are more likely to spawn tumors elsewhere in the body.

Molecular biologist Antonio García de Herreros of Pompeu Fabra University in Barcelona, Spain, has found that in a line of epithelial tumor cells, Snail binds to a stretch of DNA immediately preceding the E-cadherin gene, thereby gumming up the works and stopping E-cadherin from being produced. Without E-cadherin, the cells are less sticky. The finding suggests that Snail is responsible for the ability of the cancerous epithelial cells to bust out of their interlaced epithelial network and turn into tumors. In separate work, cell biologist M. Angela Nieto and her team at the Institute of Investigative Biomedicine in Madrid tested five mouse and seven human tumor cell lines. The most invasive cells had the most Snail and the least E-cadherin. Moreover, Snail seemed to be turning some cells from tightly packed epithelial cells back into loose mesenchymal cells, those that can break free to form tumors. Both groups describe their work in the February Nature Cell Biology.

The findings are strong evidence that Snail can cut the tether of cancer cells, says cell biologist Barry Gumbiner of Memorial Sloan-Kettering Cancer Center in New York City. Nieto suggests that the presence of Snail in a tumor sample will, like low levels of E-cadherin, alert pathologists that the tumor is likely to spread.